Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human procathepsin H was expressed in the form of inclusion bodies in Escherichia coli. Following refolding and autocatalytic activation, a recombinant cathepsin H form lacking the mini chain was produced. Removal of the mini chain completely abolished aminopeptidase activity of the enzyme and largely increased its endopeptidase activity (approximately 40-fold). Similarly to cathepsin S, Bz-FVR-AMC (k(cat)/K(m) value of 1070 mM(-1) s(-1)) was found to be the preferred substrate of recombinant cathepsin H. However, substrate inhibition was observed at a higher substrate (Z-FR-AMC, Bz-FVR-AMC) concentration. Endopeptidase activity of recombinant cathepsin H was seen also with the protein substrate insulin beta-chain with the major cleavage site between Glu13-Ala14. Recombinant human cathepsin H was inhibited by chicken cystatin, stefin A, and stefin B with the K(i) values in the range of 0.05-0.1 nM, which is slightly tighter than the inhibition of purified cathepsin H by the same inhibitors. These results thus indicate that the cathepsin H mini chain is essential for the aminopeptidase activity of the enzyme but has only a minor effect on the inhibition by cystatins.
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PMID:Recombinant human cathepsin H lacking the mini chain is an endopeptidase. 1462 98

Cysteine cathepsins play an indispensable role in proteolytic processing of the major histocompatibility complex class II-associated invariant chain (Ii) and foreign antigens in a number of antigen presenting cells. Previously it was shown that a fragment of 64 residues present in the p41 form of the Ii (p41 fragment) selectively inhibits the endopeptidase cathepsin L, whereas the activity of cathepsin S remains unaffected. Comparison of structures indicated that the selectivity of interactions between cysteine cathepsins and the p41 fragment is far from being understood and requires further investigation. The p41 fragment has now been shown also to inhibit human cathepsins V, K, and F (also, presumably, O) and mouse cathepsin L with K(i) values in the low nanomolar range. These K(i) values are sufficiently low to ensure complex formation at physiological concentrations. In addition we have found that the p41 fragment can inhibit cathepsin S too. These findings suggest that regulation of the proteolytic activity of most of the cysteine cathepsins by the p41 fragment is an important and widespread control mechanism of antigen presentation.
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PMID:Inhibitory fragment from the p41 form of invariant chain can regulate activity of cysteine cathepsins in antigen presentation. 1836 48

Cathepsin S (CatS) is a lysosomal cysteine protease belonging to the papain superfamily. Because of the relatively broad substrate specificity of this family, a specific substrate for CatS is not yet known. Based on a detailed study of the CatS endopeptidase specificity, using six series of internally quenched fluorescent peptides, we were able to design a specific substrate for CatS. The peptide series was based on the sequence GRWHTVGLRWE-Lys(Dnp)-DArg-NH2, which shows only one single cleavage site between Gly and Leu and where every substrate position between P-3 and P-3' was substituted with up to 15 different amino acids. The endopeptidase specificity of CatS was mainly determined by the P-2, P-1', and the P-3' substrate positions. Based on this result, systematically modified substrates were synthesized. Two of these modified substrates, Mca-GRWPPMGLPWE-Lys(Dnp)-DArg-NH2 and Mca-GRWHPMGAPWE-Lys(Dnp)-DArg-NH2, did not react with the purified cysteine proteases cathepsin B (CatB) and cathepsin L (CatL). Using a specific CatS inhibitor, we could further show that these two peptides were not cleaved by endosomal fractions of antigen presenting cells (APCs), when CatS was inhibited and related cysteine proteases cathepsin B, H, L and X were still active. Although aspartic proteases like cathepsin E and cathepsin D were also present, our substrates were suitable to quantify cathepsin S activity specifically in APCs, including B cells, macrophages, and dendritic cells without the use of any protease inhibitor. We find that CatS activity differs significantly not only between the three types of professional APCs but also between endosomal and lysosomal compartments.
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PMID:Quantifying cathepsin S activity in antigen presenting cells using a novel specific substrate. 1895 8

Transcriptional activity of nuclear receptors is the result of transactivation capability and the concentration of the receptor protein. The concentration of ecdysteroid receptor (EcR) isoforms, constitutively expressed in mammalian CHO cells, is dependent on a number of factors. As shown previously, ligand binding stabilizes receptor protein concentration. In this paper, we investigate the degradation of EcR isoforms and provide evidence that N-terminal degradation is modulated by isoform-specific ubiquitination sites present in the A/B domains of EcR-A and -B1. This was demonstrated by the increase in EcR concentration by treatment with carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132), an inhibitor of ubiquitin-mediated proteasomal degradation and by deletion of ubiquitination sites. In addition, EcR is degraded by the peptidyl-dipeptidase cathepsin B (CatB) and the endopeptidase cathepsin S (CatS) at the C-terminus in an isoform-specific manner, despite identical C-termini. Ubiquitin-proteasome-mediated degradation and the proteolytic action are modulated by heterodimerization with Ultraspiracle (USP). The complex regulation of receptor protein concentration offers an additional opportunity to regulate transcriptional activity in an isoform- and target cell-specific way and allows the temporal limitation of hormone action.
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PMID:N- and C-terminal degradation of ecdysteroid receptor isoforms, when transiently expressed in mammalian CHO cells, is regulated by the proteasome and cysteine and threonine proteases. 2256 80

Two cysteine proteases, cathepsin S (CatS) and cathepsin L (CatL), have been identified as the key enzymes involved in the processing of invariant chain (Ii chain) in mammals. However, little is known about the roles of fish cathepsins in the Ii chain processing. In this study, large yellow croaker cathepsin S (LycCatS) and L (LycCatL) were identified and characterized. Based on the sequence comparison and phylogenetic analysis, both LycCatS and LycCatL are highly conserved to their counterparts in teleost. These two cathepsins were constitutively expressed in all tissues and immune-related cells tested, although at different levels. Both recombinant LycCatS (rLycCatS) and LycCatL (rLycCatL) possess the typical cysteine protease activity. Like other mammalian endopeptidase cathepsins, rLycCatS and rLycCatL could be autocatalytically activated to remove propeptides and release active mature peptides. On the other hand, the autocatalytic activation of rLycCatL could be inhibited by recombinant large yellow croaker Ii chain (rLyc-TR-Ii), but the autocatalytic activation of rLycCatS was not affected by rLyc-TR-Ii. Furthermore, the activated rLycCatS can efficiently process rLyc-TR-Ii in a stepwise manner in vitro, while the activated rLycCatL can not. These data indicate that cathepsin S may be the main cathepsin involved in the Ii chain processing in bony fish.
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PMID:Cathepsin S, but not cathepsin L, participates in the MHC class II-associated invariant chain processing in large yellow croaker (Larimichthys crocea). 2647 63